title: Prevention of hemolysis-induced organ damage by nutritional activation of the vagal anti-inflammatory reflex*.
abstract: OBJECTIVE
  Acute hemolysis is associated with organ damage, inflammation, and impaired vascular function. Stimulation of the cholecystokinin-1 receptor-dependent vagal anti-inflammatory reflex with lipid-rich enteral nutrition was demonstrated to prevent tissue damage and attenuate inflammation. This study investigates the effects of nutritional activation of the vagal anti-inflammatory reflex on organ integrity, systemic inflammation, and microcirculation during hemolysis.
  
  
  METHODS
  Prospective randomized controlled study.
  
  
  METHODS
  University research unit.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Intravascular hemolysis was simulated by infusion of prelysed erythrocytes. Animals were fasted or received lipid-rich enteral nutrition. Pegylated (PEG)-CCK9A, A70104 (a cholecystokinin-1 receptor antagonist), and chlorisondamine (a nicotinic acetylcholine receptor antagonist) were applied to investigate involvement of the vagal reflex.
  
  
  RESULTS
  Nutritional intervention reduced hemolysis-related renal tubular cell damage, hepatocyte damage, ileal leakage of horseradish peroxidase, and bacterial translocation compared with food deprivation (all p < 0.05). Also circulating interleukin (IL)-6 levels were decreased by enteral nutrition (p < 0.05). Blockage of the cholecystokinin-1 receptor or the nicotinic acetylcholine receptor reversed the protective nutritional effects compared with vehicle (p < 0.05), whereas PEG-CCK9 mimicked the impact of enteral feeding in fasted animals (p < 0.05). Furthermore, nutritional intervention increased renal, hepatic, and intestinal blood flow compared with fasting (all p < 0.05), as evaluated using fluorescent microspheres.
  
  
  CONCLUSIONS
  Nutritional activation of the vagal anti-inflammatory reflex preserves tissue integrity and attenuates systemic inflammation in a rodent model of acute hemolysis. In addition, lipid-rich nutrition improves renal, hepatic, and intestinal microcirculation. These findings implicate stimulation of the autonomic nervous system by nutritional means as a potential therapy to prevent complications of acute hemolysis. (Crit Care Med 2013; 41:e361-e367).
authors.affiliation: 1Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands. 2Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. 3Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, Maastricht, The Netherlands. 4Department of Surgery, Atrium Medical Center, Heerlen, The Netherlands.
authors.forename: Jacco J
authors.initials: JJ
authors.lastname: de Haan
authors.forename: Iris Vermeulen
authors.initials: IV
authors.lastname: Windsant
authors.forename: Tim
authors.initials: T
authors.lastname: Lubbers
authors.forename: Sebiastiaan J
authors.initials: SJ
authors.lastname: Hanssen
authors.forename: M'hamed
authors.initials: M
authors.lastname: Hadfoune
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.forename: Jan-Willem M
authors.initials: JW
authors.lastname: Greve
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D000818:Animals; D002714:Chlorisondamine / Q000494:pharmacology; D004041:Dietary Fats; D004064:Digestive System / Q000503:physiopathology*; D005502:Food; D006461:Hemolysis / Q000502:physiology*; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D018836:Inflammation Mediators; D018733:Nicotinic Antagonists; D011804:Quinolines; D011949:Receptors, Cholecystokinin; C063047:A 65186; D002714:Chlorisondamine